The present invention relates to novel heterocyclic carboxamides to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the present invention include selective agonists and antagonists of serotonin 1 (5-HT.sub.1) receptors, specifically, of one or both of the 5-HT.sub.1A and 5-HT.sub.1D receptors. They are useful in treating or preventing migraine, depression and other disorders for which a 5-HT.sub.1 agonist or antagonist is indicated.
European Patent Publication 434,561, published on Jun. 26, 1991, refers to 7-alkyl, alkoxy, and hydroxy substituted-1-(4-substituted-1-piperazinyl)-naphthalenes. The compounds are referred to as 5-HT.sub.1 agonists and antagonists useful for the treatment of migraine, depression, anxiety, schizophrenia, stress and pain.
European Patent Publication 343,050, published on Nov. 23, 1989, refers to 7-unsubstituted, halogenated, and methoxy substituted-1-(4-substituted-1-piperazinyl)naphthalenes as useful 5-HT.sub.1A ligand therapeutics.
PCT publication WO 94/21619, published Sept. 29, 1994, refers to naphthalene derivatives as 5-HT.sub.1 agonists and antagonists.
PCT publication WO 96/00720, published Jan. 11, 1996, refers to naphthyl ethers as useful 5-HT.sub.1 agonists and antagonists.
European Patent Publication 701,819, published Mar. 20, 1996, refers to the use of 5-HT.sub.1 agonists and antagonists in combination with a 5-HT re-uptake inhibitor.
Glennon et al., refers to 7-methoxy-1-(1-piperazinyl)-naphthalene as a useful 5-HT.sub.1 ligand in their article "5-HT.sub.1D Serotonin Receptors", Clinical, 22, 25-36 (1991).
Glennon's article "Serotonin Receptors: Clinical Implications", Neuroscience and Behavioral Reviews, 14, 35-47 (1990), refers to the pharmacological effects associated with serotonin receptors including appetite suppression, thermoregulation, cardiovascular/hypotensive effects, sleep, psychosis, anxiety, depression, nausea, emesis, Alzheimer's disease, Parkinson's disease and Huntington's disease.
World Patent Application WO 95/31988, published Nov. 30, 1995, refers to the use of a 5-HT.sub.1D antagonist in combination with a 5-HT.sub.1A antagonist to treat CNS disorders such as depression, generalized anxiety, panic disorder, agoraphobia, social phobias, obsessive-compulsive disorder, post-traumatic stress disorder, memory disorders, anorexia nervosa and bulimia nervosa, Parkinson's disease, tardive dyskinesias, endocrine disorders such as hyperprolactinaemia, vasospasm (particularly in the cerebral vasculature) and hypertension, disorders of the gastrointestinal tract where changes in motility and secretion are involved, as well as sexual dysfunction.
G. Maura et al., J. Neurochem, 66 (1), 203-209 (1996), have stated that administration of agonists selective for 5-HT.sub.1A receptors or for both 5-HT.sub.1A and 5-HT.sub.1D receptors might represent a great improvement in the treatment of human cerebellar ataxias, a multifaceted syndrome for which no established therapy is available.